rs3027875

Positions:

chrX-153950388-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005334.3(HCFC1):c.5859C>T(p.Cys1953Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 111,874 control chromosomes in the GnomAD database, including 9,743 homozygotes. There are 13,393 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 9743 hom., 13393 hem., cov: 24)

Exomes 𝑓: 0.58 ( 136906 hom. 204100 hem. )

Failed GnomAD Quality Control

Consequence

HCFC1
NM_005334.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.400

Variant links:

Genes affected

HCFC1 (HGNC:4839): (host cell factor C1) This gene is a member of the host cell factor family and encodes a protein with five Kelch repeats, a fibronectin-like motif, and six HCF repeats, each of which contains a highly specific cleavage signal. This nuclear coactivator is proteolytically cleaved at one of the six possible sites, resulting in the creation of an N-terminal chain and the corresponding C-terminal chain. The final form of this protein consists of noncovalently bound N- and C-terminal chains. The protein is involved in control of the cell cycle and transcriptional regulation during herpes simplex virus infection. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

HCFC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant X-153950388-G-A is Benign according to our data. Variant chrX-153950388-G-A is described in ClinVar as [Benign]. Clinvar id is 95281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153950388-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCFC1	NM_005334.3 linkuse as main transcript	c.5859C>T	p.Cys1953Cys	synonymous_variant	24/26	ENST00000310441.12	NP_005325.2	P51610-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HCFC1	ENST00000310441.12 linkuse as main transcript	c.5859C>T	p.Cys1953Cys	synonymous_variant	24/26	1	NM_005334.3	ENSP00000309555.7	P51610-1
HCFC1	ENST00000369984.4 linkuse as main transcript	c.5994C>T	p.Cys1998Cys	synonymous_variant	24/26	5		ENSP00000359001.4	A6NEM2
HCFC1	ENST00000444191.5 linkuse as main transcript	c.1584C>T	p.Cys528Cys	synonymous_variant	8/10	5		ENSP00000399589.1	H7C1C4

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

46362

AN:

111821

Hom.:

9747

Cov.:

AF XY:

0.393

AC XY:

13389

AN XY:

34033

show subpopulations

Gnomad AFR

AF:

0.0854

Gnomad AMI

AF:

0.696

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.581

Gnomad EAS

AF:

0.00394

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.567

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.644

Gnomad OTH

AF:

0.414

GnomAD3 exomes

AF:

0.426

AC:

75791

AN:

178057

Hom.:

13807

AF XY:

0.434

AC XY:

28382

AN XY:

65325

show subpopulations

Gnomad AFR exome

AF:

0.0706

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.557

Gnomad EAS exome

AF:

0.000817

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.600

Gnomad NFE exome

AF:

0.648

Gnomad OTH exome

AF:

0.490

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.576

AC:

631434

AN:

1096360

Hom.:

136906

Cov.:

AF XY:

0.563

AC XY:

204100

AN XY:

362246

show subpopulations

Gnomad4 AFR exome

AF:

0.0743

Gnomad4 AMR exome

AF:

0.217

Gnomad4 ASJ exome

AF:

0.549

Gnomad4 EAS exome

AF:

0.000696

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.604

Gnomad4 NFE exome

AF:

0.659

Gnomad4 OTH exome

AF:

0.506

GnomAD4 genome

AF:

0.414

AC:

46346

AN:

111874

Hom.:

9743

Cov.:

AF XY:

0.393

AC XY:

13393

AN XY:

34096

show subpopulations

Gnomad4 AFR

AF:

0.0852

Gnomad4 AMR

AF:

0.297

Gnomad4 ASJ

AF:

0.581

Gnomad4 EAS

AF:

0.00395

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.567

Gnomad4 NFE

AF:

0.644

Gnomad4 OTH

AF:

0.407

Alfa

AF:

0.535

Hom.:

6466

Bravo

AF:

0.380

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 19, 2013	- -

Methylmalonic acidemia with homocystinuria, type cblX

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.26

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over